The acute phase of inflammation is characterized by a variety of humoral and cellular responses including enhanced granulocyte production, migration and metabolic activity leading to phagocytosis, enzyme release and tissue damage, and dramatic increases in plasma proteins, including C-reactive protein (CRP). CRP mediates activation of the classical complement pathway and modulates cellular functions, including those of granulocytes. CRP has been reported to mediate C-dependent adherence and phagocytosis in the abscence of serum, to have no effect on bactericidal activity of PMN in the presence or absence of serum and to contribute to enhanced random motility of normal peripheral blood leukocytes. The presence of CRP in circulation coincides with reticuloendothelial system activation however, the protein does not appear to accumulate at inflammatory sites. This could be indicative of a role for CRP providing for CRP modulation of PMN activity and/or PMN regulation of CRP metabolism or clearance. The proposed research will define the relationship between CRP binding, specificity and conformational alterations and C-dependent and C-independent PMN stimulation, the effects of CRP on PMN membrane activity with an emphasis on Ca-dependent regulation of motile and secretory functions and the interactions between CRP and the neutral proteases of the granulocyte with special reference to the effects of CRP on protease enzymic activity and the capacity of the proteases to generate biologically active intermediates from CRP.